Compounds and methods for inhibiting .beta.-protein filament formation and neurotoxicity

Methods of treating an individual with Alzheimer's Disease by administering to the patient a therapeutically effective dose of a compound which interferes with the interaction between Alzheimer .beta.-protein and Apolipoprotein E4 or .alpha..sub.1 -antichymotrypsin, thereby suppressing the formation of Alzheimer .beta.-protein filaments and the neurotoxic effects of these filaments. The present invention also refers to methods of screening for compounds which are effective drugs for treating Alzheimer's disease. These methods comprise screening for compounds which suppress the formation of Alzheimer .beta.-protein filaments in the presence of promoting factors and which suppress the neurotoxic effects of these filaments formed in the presence of promoting factors.

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Claims

1. An oligopeptide, wherein the oligopeptide is selected from the group consisting of A.beta..sub.2-9, a fragment of A.beta..sub.2-9 or a modified fragment of A.beta..sub.2-9, wherein the oligopeptide binds.alpha..sub.1 -antichymotrypsin.

2. An oligopeptide, wherein the oligopeptide is A.beta..sub.2-9 or a fragment thereof, wherein the oligopeptide binds.alpha..sub.1 -antichymotrypsin.

3. The oligopeptide of claim 2, wherein the oligopeptide is A.beta..sub.2-9.

4. An oligopeptide, wherein the oligopeptide is a fragment of A.beta..sub.1-12, or a modified-fragment of A.beta..sub.1-12, wherein the oligopeptide binds.alpha..sub.1 -antichymotrypsin, with the proviso that the oligopeptide is not A.beta..sub.1-10.

5. The oligopeptide of claim 4 wherein the oligopeptide is A.beta..sub.2-10, A.beta..sub.2-11, A.beta..sub.1-11, or A.beta..sub.1-9.

6. An oligopeptide, wherein the oligopeptide is a fragment of A.beta..sub.12-28 or a modified fragment of A.beta..sub.12-28, wherein the oligopeptide binds ApoE4, with the proviso that the oligopeptide is not A.beta..sub.17-20 or A.beta..sub.18-28.

Referenced Cited
U.S. Patent Documents
4303592 December 1, 1981 Laura et al.
4666829 May 19, 1987 Glenner et al.
Foreign Patent Documents
2071661 September 1981 GBX
WO 92/03474 March 1992 WOX
92/03542 March 1992 WOX
92/03474 March 1992 WOX
WO 93/15112 August 1993 WOX
WO 94/09364 April 1994 WOX
Other references
Patent History
Patent number: 5780587
Type: Grant
Filed: Apr 6, 1995
Date of Patent: Jul 14, 1998
Assignee: President and Fellows of Harvard College (Cambridge, MA)
Inventor: Huntington Potter (Boston, MA)
Primary Examiner: Toni R. Scheiner
Assistant Examiner: Sheela J. Huff
Law Firm: Hamilton, Brook, Smith & Reynolds, P.C.
Application Number: 8/417,937